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Investigating inflammatory processes of plaque destabilization using proteomics
Lasse Lorentzen
SSAR 2022
Extracellular matrix remodeling in atherosclerosis
Extracellular matrix remodeling in atherosclerosis
Synthesis of new extracellular matrix (ECM) proteins
Degradation of “old” ECM proteins
Remodeling of the vascular ECM takes place under atherosclerotic conditions
Hypothesis:
Remodeling of the vascular ECM is a key driver in plaque destabilization
ECM degradation by proteolytic enzymes
ECM degradation by proteolytic enzymes
ECM degradation by proteolytic enzymes
Proteomics investigation of ECM remodelling
Proteomics workflow
Study design
21 symptomatic plaques from the carotid artery
7 Hard, 7 Mixed, 7 Soft plaques
Compared by proteomics
Differentially regulated proteins
Over-representation analysis
Over-representation analysis
N-terminomics investigation of protelytic ECM remodelling
Proteomics workflow
ECM degradation by proteolytic enzymes
Differentially regulated free N-termini
Most regulated free N-termini are non-canonical
Degradation of Collagen type VI
Degradation of other Collagens
Degradation of Fibronectin
Degradation of other basement membrane proteins
Sequence motif analysis
Summary
Soft plaques are associated with lower level of ECM proteins
Soft plaques are associated with increased abundance of proteolytic enzymes
ECM proteins are subject to proteolytic degradation
ECM degradation is consistent with MMP activity
Thanks
Prof. Michael Davies
Prof. Henrik Sillesen, Prof. Jonas Eiberg, Karin Yeung
Christine Chuang
Protein Oxidation Group
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